London – Another UK biotech company was taken over when Novartis signed a recommended all-cash offer worth Euro435 million for the antibiotics specialists Neutec pharma. The Swiss pharma giant paid more than twice of the Manchester-based company’s market capitalization before the takeover approach. Buying Neutec gives Novartis access to two advanced stage antibody products for serious hospital-acquired infections: Mycograb, for treating systemic fungal infections and Aurograb, for treating methicillin-resistant Staphylococcus aureus. Daniel Vasella, CEO of Novartis, said the products “promise to dramatically improve treatments in the area and will also enable Novartis to strengthen its biologics pipeline and anti-infective drug portfolio.” Mycograb has been filed in Europe and has been approved for compassionate use, while Aurograb is in phase III. NeuTec has retained 100% ownership of its products. The buyout is a big payday for the founders Ruth Mathews and James Burnie, who still own a 7% stake. During the takeover negotiations the founders secured NeuTecs operations at the current facility in Manchester for at least two years. The sale of the company came just three weeks after AstraZeneca agreed to buy Cambridge Antibody for Euro1.1 billion. Besides the Neutec deal the antibiotics market has seen amany known players disappear. One of the most prominent was the US-based Vicuron, bought by Pfizer for $1.9 billion. New companies have nevertheless emerged as Roche (Basilea), Sanofi-Aventis (Novexel), Sandoz (Nabriva) and Bayer (Aicuris) span out their infectious disease businesses.
A group of 13 internationally renowned stem cell scientists warn in a letter to Nature (2011, Vol. 572, S. 418) that the field is under serious threat from a case which is before the European Court of Justice. The academics said...
A group of 13 internationally renowned stem cell scientists warn in a letter to Nature (2011, Vol. 572, S. 418) that the field is under serious threat from a case which is before the European Court of Justice. The academics said that a change in EU law could "wipe out" much of the biotechnology industry. The judges are considering a test case in which the environmental organisation Greenpeace challenges the patents the German stem cell pioneer Oliver Brustle is maintaining on stem cell cultivation. The academics are concerned because Yves Bot, the court's advocate general who provides independent guidance, said in a statement on March 10 that patenting any use of cells derived from human embryos breached ethical principles. Although the French judge's opinion is not binding, the court follows his advice in eight out of 10 judgments. A corresponding ruling could effectively outlaw the use of human embryos for commercial purposes. In their letter, the 13 researchers stated that much of the ongoing research would then be moved to China and the US. The 13 include Ian Wilmut, director of the MRC Centre for Regenerative Medicine at the University of Edinburgh and Austin Smith, director of the Wellcome Trust Centre for Stem Cell Research in Cambridge. Smith called Mr Bot’s opinion “astonishing and shocking”, and said that without the contribution of industry that patents made possible, the development of stem cell therapies could stop. “If the European Court of Justice was to follow this opinion then the reality ... is that all patents in Europe that involve human embryonic stem cells will be eliminated,” he said. “Other patents will apply in the United States, China and Japan, so this will put Europe at a huge disadvantage. It will effectively wipe out the European biotech industry in this area.” More than 100 patents on embryonic stem cell products have already been filed in Europe.
Parma - The European Food Safety Authority (EFSA) has set its eyes on saving genes from damage by substances in food and feed. Before 31 May 2011, stakeholders and interested parties can comment on a draft opinion from EFSA's...
Parma - The European Food Safety Authority (EFSA) has set its eyes on saving genes from damage by substances in food and feed. Before 31 May 2011, stakeholders and interested parties can comment on a draft opinion from EFSA's Scientific Committee. In the paper, an effort is made to overhaul the risk assessment of substances used in the food and feed chain and contribute to further harmonisation of genotoxicity testing across EFSA’s Scientific Panels. The opinion states that in order to provide an adequate evaluation of the genotoxic potential of a substance, it is necessary to assess gene mutations, structural and numerical chromosomal alterations, as all these aspects are known to be implicated in carcinogenesis and the development of heritable diseases. It recommends that adequate coverage of all these aspects can be obtained through the use of two in vitro tests in the first instance with follow-up in vivo testing if necessary. Further details can be gathered in the online version of the draft. In finalising its opinion, the Scientific Committee promises to take into account all comments received during the public consultation. A summary report will be published on the EFSA website along with the final opinion expected to be completed in the autumn.
Brussels – Assessment of the socio-economic impact of GMO cultivation in the EU is currently hampered by the lack or absence of statistically relevant information, says a brand-new report tabled by the European Commission. What’s...
Brussels – Assessment of the socio-economic impact of GMO cultivation in the EU is currently hampered by the lack or absence of statistically relevant information, says a brand-new report tabled by the European Commission. What’s more, existing information is often based on already preconceived ideas about GMO cultivation, according to the Commission. The 11-page report and a 97-page Commission staff working document present an analysis of the socio-economic dimensions of GMO cultivation as reported in the international scientific literature and in the conclusions of research projects funded under the EU’s Framework Programmes for research (FP7). "With the publication of this report, the Commission is delivering one of the last pending requests made by the Environment Council in December 2008“ stressed Health and Consumer Policy Commissioner, John Dalli. „The document has been compiled on the basis of data and information provided by the Member States. I firmly believe that this report creates an opportunity: It is now up to the Member States, the Commission, the European Parliament and all interested parties, to fully grasp the report’s findings and embark on an objective discussion on the potential role of socio-economic factors in the management of GMO cultivation in the European Union." The report outlines that the experience with GMO cultivation in Europe is admittedly limited because it is only 0.06% of the global GMO acreage which was 148.1 million hectares in 2010. The consequence is that data on the ex-post socio-economic impacts of GMO cultivation is currently very limited. Existing studies show that when the weed or pest pressure is high, farmers cultivating herbicide-tolerant and pest-resistant Bt GM crops could benefit from higher yields. From international literature and input from the EU member states, the Commission’s report postulates that economic analyses provide a good picture of the economic impact at farm level world-wide. Available information on social impacts and effects along the food chain is rather limited, if not absent. The report provides a review of the findings of EU funded research projects addressing socio-economic perspectives of GMO cultivation (CO-EXTRA, SIGMEA, CONSUMERCHOICE). The Commission claimed the report to be the starting point for the Member States, the Commission, the European Parliament and all stakeholders to discussions on an objective basis. The Commission proposes defining a „robust set of factors and indicators to capture the socio-economic consequences of GMO cultivation across the EU and along the food chain. In December 2008, the Environment Council asked the Member States to collect and exchange relevant information on the socio-economic implications of GMO cultivation across the food chain. It also asked the Commission to prepare, on the basis of this information, a report for due consideration and further discussion.
Five years ago, the European Commission adopted the Health Claims Regulation (EC 1924/2006) to protect consumers from misleading claims about positive health effects of foods. According to the Regulation, health claims must be...
“The reason for our statement (www.gut-health.eu) is that we are concerned about the fact that a number of fundamental and clinical studies – which clearly demonstrate a beneficial effect of probiotics – cannot be translated into a health claims,” said the head of the initiative, Ger Rijkers from UMC Utrecht. “The EFSA has rejected every single gut and immune system claim. That disqualifies all of the good research that has been done. If you reject all claims, than you consider every product equal – both the product with a lot of research behind it and the one without any scientific evidence.” Last autumn, the EFSA rejected a claim that the probiotic drink Yakult can help prevent colds. By January, the authority said that the drink Actimel, produced by French probiotics world market leader Danone, may not sport claims it prevents diarrhea caused by infections with Clostridium difficile. Those evaluations are in sharp contrast to a current meta-analysis carried out by researchers from the industry-independent Cochrane Collaboration. After analysing 63 clinical trials involving over 8,000 people suffering from infectious diarrhea, Cochrane found that probiotics significantly reduced stool frequency, duration of the condition, and reduced the risk of diarrhea lasting four or more days by 60% (Cochrane Database of Systematic Reviews, doi: 10.1002/14651858.CD003048.pub3). “No more industry money is being invested in the research of a rejected health claim,” Rijkers told EuroBiotechNews. “Why should you put money into an area when the EFSA says it is complete nonsense?”
Researchers call for modification of the Regulation
The group behind Rijkers wants “crystal-clear rules” – including what kind of data the EFSA expects exactly – as well as the establishment of a kind of pre-assessment of submissions, as is common with pharmaceutical authorities. According to them, the evaluation criteria are unclear because the EFSA experts keep saying that they are analysing claims on a case-by-case basis and that it is also a learning process for them. “This implies that there are no strict rules – a bad experience for those who submitted their claims first,” explains Rijkers. Additionally, they are striking at the roots of the Regulation, which clearly excludes clinical endpoints from the assessment of the claims. “If you want to develop a product that prevents diarrhea, you can’t use diarrhea as an endpoint ,” says Rijkers. “But from a scientific standpoint, it would make sense to use this clinical endpoint.” Currently, the EU rules demand proof of health benefits by the establishment of biomarker-based cause-relationships in healthy people. “That’s exactly the problem. You can’t become healthier than healthy,” says food expert Andreas Hahn from Hanover University. According to Rijkers, it is extremely challenging to find biomarkers demonstrating that a food ingredient supports homeostasis, the optimal state of health. “Up until now, the EFSA has mostly approved health claims that rely on established biomarkers but less innovative approaches,” says Hahn.
Advantage for global players
According to Hahn, the strict criteria used by the EFSA clearly penalise innovative SMEs, which frequently do not have the financial resources to pay for expensive human trials. However, one small company has demonstrated it is possible to get approvals for complex food products. Liverpool-based Provexis put about £2m into 10 clinical studies with a total of 400 subjects to demonstrate that their tomato extract Fruit Flow® prevents aggregation of platelets by up to 27%. The promise of preventing the formation of blood clots – and subsequent heart attacks and strokes – brought the start-up a licensing deal with DSM Nutritional Products. Provexis COO Steve Morrison told EuroBiotechNews that in pursuing approval, it’s important to have a strong and well-detectable endpoint, an exact characterisation of the product, and well-designed human studies.
Obscure evaluation results
Some EFSA assessments remain obscure. In January, the authority rejected a health claim submitted by Hahn in 2008 that – put simply – says drinking water prevents the aftereffects of dehydration. “We were surprised the EFSA was unwilling to accept a cause-relationship that is clear to every student of physiology,” says Hahn, who believes that the agency has not met its goal of coming to decisions based exclusively on scientific facts. If the claim is rejected by the European Commission, Hahn is considering bringing the case to the European Court of Justice. Rijkers has planned to meet MEPs and the Commission to discuss his proposals.
Personalised medicine – the buzzword that describes selecting and treating defined patient subpopulations that respond to a specific drug treatment, thereby allowing physicians to pursue more stratified medicine. Pharma and...
Personalised medicine – the buzzword that describes selecting and treating defined patient subpopulations that respond to a specific drug treatment, thereby allowing physicians to pursue more stratified medicine. Pharma and diagnostics giant Roche is a pioneer in this field, which seems to have become the new paradigm in drug development due to its potential to reduce failure and cost in clinical development. EuroBiotechNews spoke with Roche Pharma AG chief Dr. Hagen Pfundner about the company’s strategy in Personalised Healthcare – a topic he will present in depth in June at the PerMediCon conference in Cologne, a meeting for key figures in the field. Euro|BioTech|News Dr. Pfundner, at PerMediCon you’re going to look at company strategies in the field of personalised healthcare. Why is Roche – and increasingly other pharmaceutical companies – so involved with this field?
Pfundner: Today’s medicines have one problem in common. Their success rate is suboptimal. Overall, roughly 30-50% of the patients do not profit from the medicines. Thus, our challenge as an industry is to improve the effectiveness of our therapeutics. And this has two dimensions – decreasing the risk of unwanted side effects for patients and increasing efficacy. And that’s why the industry is on this journey. Advances in biotechnology, diagnostics, biomarker research and targeted medicines enable us today to approach the development of medicines differently. Industry is shifting to release the potential of scientific knowledge and turn it into medicines that work better for patients.
Euro|BioTech|News That sounds good, but to find and to validate a predictive biomarker today is challenging. Where exactly does the industry stand today on the path to personalised therapies?
Pfundner: This journey began years ago. Thus it is not a a quick fix. It was a journey that co-incided with the evolution of science. The Big Bang in modern personalised medicine was the development of Herceptin® as a targeted breast cancer medicine. First it seemed we had developed a medicine that showed limited efficacy. But by identifying a subgroup of patients carrying a defined biomarker, we could pick out the 20% that would benefit substantially. At that point we recognised that we would need more basic
research with a focus on molecular targets. We needed the capabilities from our diagnostics groups together with our pharma R&D to bring these two forces together. And now the strategic approach has been turned into a business model. Today Roche is at a stage where personalised medicine is no longer a strategic vision – it is our base business model. Euro|BioTech|News Are you already able to measure the success of this approach in terms of reducing failure in clinical trials?
Pfundner: This is probably where a large and significant benefit may be in the future. But we have already learned lessons that transform the speed, size and magnitude of our clinical development programme. Today, we already have medicines that fit the purpose of personalised medicines. Herceptin is one example. PEGylated interferons versus HCV – stratifying patient populations and shortening treatment duration as well as reducing side effects – is already occurring with products from our company and other companies. A more recent breakthrough in our late-stage development was the stratification of patients with malignant melanoma that carry a BRAF mutation – about 50-60% of the melanoma patients have a very aggressive form of skin cancer. We can identify that patient population, and within it the response rate is exceptionally high. Thus, we not only reduce the size of the clinical programme, we bring it forward faster and we reduce the associated risk of failure by stratifying patient populations. If you have a shorter development time, this improves the time for product exclusivity and increases your patent. So it reduces the commercial risk, and it also leads – this is our hope – to a clearer benefit proposition for patients, therefore increasing the chances of commercial success. Euro|BioTech|News Risk reduction is a positive effect. But how does the reduced population size
affect a company’s return on investment?
Pfundner: I think this is where a shift in thinking has taken place within the industry and within society. The name of the game today is incremental patient benefit over currently available therapies. And that patient benefit is what gives you a chance of successfully marketing and commercialising a product today. If this benefit increases disproportionately versus the available patient population, then you still have a significant business case. Take Herceptin. It’s a niche product; it addresses only 20% of all breast cancer patients. But it makes CHF5 bn per year. Shrinking populations do not necessarily mean you can’t have a good ROI. But today, you have to justify a premium price with a premium benefit. And that benefit is more likely to be shown in a smaller patient population. With this approach an individual treatment might be more expensive on the surface. How-
ever, the benefit that comes with that individual treatment option is a much bigger benefit, because you reduce the 50% failure rate and side effects. Euro|BioTech|News What are the main challenges on the pathway to bringing personalised treatments to the market? Pfundner: I think there are two dimensions. I would call one of them the “inside dimension” and the other “outside dimension”. The inside dimension is that you need to have the capability and people to develop and commercialise an individualised treatment consisting of a targeted medicine and a companion diagnostic. That’s where Roche has a strategic advantage, because we have worked on that capability for many years. Now we see the fruits of our labor. The outside dimension is the regulatory framework, the reimbursement institutions and the stakeholders (physicians) that have to deal with these new technologies. You can see for example in Germany that personalised medicines are already being recognised at the political level. The government has made personalised medicines a priority in its coalition contract. Furthermore, regulatory bodies have already invited us to discuss preparatory reviews of our personalised medicines. The regulatory authorities already are working on a development framework in that regard. And that trend is international. Currently we have six late-stage molecules under development together with a companion diagnostic. So personalised medicine is a reality in clinical development. Another reality in the regulatory framework, however, is that there are different paths for approving a diagnostic and for approving a medicine. We need to synchronise the approvals. The next hurdle after regulatory
authorisation of a personalised medicine is reimbursement. Again, there’s a different path getting it for a diagnostic versus a pharma medicine. And again, we will be pacesetters in this regard.
Euro|BioTech|News So where is the challenge?
Pfundner: The challenge is that this has not become standard routine. Every time you take a new approach, you are breaking new ground, and this carries greater risks for the sponsor and the regulator. I would say there is the willingness to do it, but the challenge lies in the readiness. We are getting ready but we aren’t there yet. A better patient stratification could also help with reimbursement be-
cause it makes the picture for those who benefit and those who do not much clearer. The third big challenge is the physician, because it requires significant education to deal with personalised medicines that will transform the way we administer medicines. Euro|BioTech|News How does acceptance look on that
Pfundner: I think the more tailored a medicine is, the higher the acceptance. The moment the physician decides to prescribe a medicine, he or she is making a promise to the patient – I can help! If doubt is cast on that promise – that you may or may not respond to the therapy – both the physician and the patient are in a difficult position. So, the more we can take away that doubt the higher the acceptance becomes. Euro|BioTech|News How will personalised medicines transform pharmaceutical markets, and in which areas?
Pfundner: There are areas where personalised medicines – or better-stratified medicines – could fit the purpose better than in other areas. For example, you don’t need a genetic profile for a painkiller, because you can dose titrate and the pain is gone.
So there are areas that will not need a biomarker or a companion diagnostic. In areas such as oncology, we’re learning more about the biology and the pathways we can specifically target. But it’s still a long shot. So I personally believe we will see more personalised medicines in the next 10 years. It will be a steady approach. There will be setbacks and successes.
Dr. Hagen Pfundner (5o) is General Manager at Roche Pharma in Grenzach-Wyhlen. The pharmacist started his industry carreer at Roche Pharma AG (Germany) in sales and marketing (1992). Three years later he took over the responsibility as Global Business Leader Inflammatory & Bone Diseases at F. Hoffmann-La Roche Ltd., Switzerland. From 1998 to 2001 he worked at Hoffmann-La Roche Ltd., Canada. As Vice President he was responsible for marketing & strategic planning & specialty care products. In 2001 Hagen Pfundner returned to F. Hoffmann-La Roche Ltd. where he was Global Business Director Virology and a member of the Global Pharma Business Leadership Team. In 2003 he became General Manager of Roche Pharma AB (Sweden). Since 2006 Pfundner holds his current position.
Stem-cell based therapies and drug screening tests are being developed all over the world – but they won’t be in Europe if the 13 Grand Chamber judges of the European Court of Justice (ECJ) in Luxembourg follow a recommendation...
For EU researchers funded by tens of millions of euros to develop therapeutic approaches or drug-screening tests based on blastocyst-derived stem cells in the past, this is an unfavourable scenario. “It’s the worst possible outcome,” said Oliver Brüstle (University of Bonn), who has been sued by Greenpeace for filing a patent in 1991 that involves turning hESCs into oligodendrocytes, the cells that produce the myelin sheath around neurons that disappear in patients with multiple sclerosis. “For companies that want to commercialise stem cell-based inventions, this is bad news. It means they can no longer protect their know-how in Europe,” says stem-cell researcher Jürgen Hescheler, who kicked off an EUR8m EU project in January pioneering the replacement of animal repeat-dose toxicity compound testing with hESC-derived cell-based assays. Hescheler’s project is part of the joint EUR50m SEURAT initiative sponsored by the EU and the European cosmetics industry to develop hESC-derived in vitro tests to replace animal testing. The EU companies involved include Swedish hESC specialist CellArtis AB, Britain’s AstraZeneca, French firm Cellectis SA and Italy’s Avantea SRL.
iPSCs – a possible alternative?
If successful, the ECJ’s move could rapidly become a problem for European companies. Last November the UK-based stem-cell branch of GE Healthcare launched the world’s first hESC-derived beating heart cells for high-throughput screening of the cardiotoxic side effects that account for 10% of all clinical study terminations (see EuroBiotechNews 11-12/2010). Unlike primary heart cells or animal cardio-models, GE’s cardiomyocytes can be produced in quantities sufficient to allow drug candidate screening. It’s the first time such a step has been possible. Roche is also planning to get involved in the promising field. The company just established preclinical toxicity testing with mouse cardiomyocytes on its newly launched RCTA Cardio Instrument, which allows real-time monitoring of the cells over several days. The next logical step is to use human-cell models of cardiotoxicity. Like other big players, Roche has established partnerships to build expertise in both the differentiation of hESCs and human induced pluripotent stem cells (hiPSCs), which can be reprogrammed by a cocktail of growth factors from human somatic cells. hiPSCs are ethically preferable to hESCs in drug testing. However, three independent research groups reported in March (Nature 471, 58-72) that hiPSCs showed genetic and epigenetic abnormalities that dramatically limit their suitability.
On both sides of the Atlantic, the past year has seen a number of developments that stand to make obtaining and enforcing biotechnological patents more difficult. Some of this development is still in flux, or has not been...
On both sides of the Atlantic, the past year has seen a number of developments that stand to make obtaining and enforcing biotechnological patents more difficult. Some of this development is still in flux, or has not been confirmed by higher instances. But the recent developments are notable for the trend they represent: whether here in Europe or in the US, biotech inventions seem to be fighting an uphill battle. In March 2010, a New York District Court invalidated claims of a US patent owned by Myriad Genetics. The claims were directed, among other things, at the breast cancer genes BRCA1 and -2. Although product claims directed to isolated genetic sequences as such have been routinely granted for many years, the court held that the genes were products of nature and were therefore not patentable inventions. Myriad has appealed the decision, and a ruling from the Court of Appeals of the Federal Circuit (CAFC) is expected soon. The appealed decision endangers the ability of applicants to obtain patent protection for genetic sequences isolated from natural sources. Several months later, the EU Court of Justice (ECJ) ruled against Patentee Monsanto’s ability to enforce one of its European patents covering the genetic sequence of an enzyme. The genetic sequence had been imported into the EU in soy meal. The ECJ cited the EU Biotech Directive, which states that the patent protection for genetic information extends to all material in which such information is contained and performs its function. The ECJ held that the soy meal was dead material in which the claimed sequence could not perform its function, and stated that no absolute product protection was possible without a corresponding function. The Monsanto decision calls into question the basic concept that product protection is absolute. Most recently (March 2011), the Advocate General of the ECJ presented the court with his proposal for how the EU Biotech Directive’s exclusion of patentability for the human body in its individual phases of development should be interpreted. In his view, the exclusion should encompass any cells that could develop into a human being (e.g. totipotent stem cells) or that are taken from an embryo. Should the ECJ follow the Advocate General’s interpretation (which is likely), applicants pursuing stem cell claims could experience a major impediment in obtaining patents to such subject matter. As mentioned, some of the above developments are still in flux. But the least that can be said is that the hurdles to obtain patents for biotech inventions have increased in the past year. Will this be modified in future decisions? More to come.
Brussels – For the greater good of Brussels and the development of agricultural research and innovation, we decided to extend our horizons a little this issue. Let's turn our attention first to a very useful report from the UK:...
Brussels – For the greater good of Brussels and the development of agricultural research and innovation, we decided to extend our horizons a little this issue. Let's turn our attention first to a very useful report from the UK: ‘The Future of Food and Farming: Challenges and choices for global sustainability’, published by the Government Office for Science. It focuses on the critical issue of food security for Europe, already manifest in increased food prices and more political, economic and climatic uncertainty. The study is a good wake-up call for Europe to take a global planning approach to food production. Few elements of European food production are independent of global influence, and Europe must look hard at how its own industry develops in response to global challenges. The upshot of the report is that food production can’t be changed a little, it has to be changed a lot. It also has to be changed now if comfortable Europe is to stay comfortable, and 925 million starving people in other parts of the world are to at least acquire subsistence-level nourishment. What many consumers and policy-makers in Europe see when they look at agriculture is thousands of years of history and integration with the land which grows our food – conveniently overlooking the fact that the process is resource-intensive and the source of significant greenhouse gas emissions, particularly in animal husbandry. Why am I talking about this? Because Europe has all the technology, knowledge and ability to change agricultural production for the better on a global scale, and should be bold enough to take on misled proponents of an often false rural ideal. The potential impact of biotechnology applied to agricultural production is huge. GMOs are still a tiny, overexposed fragment of biotech, but GM technology cannot be ignored as a tool for reducing chemical input. Fortunately, the European Commission is finally getting off the fence where the science is sound and the arguments against are based on political popularity contests rather than facts and figures. It's early days though. The arguments are almost literally chicken-feed at the moment in Europe, and the big discussions are yet to come. But when it comes to biotechnology in food production, GMOs are just the beginning. Throughout the food chain, biotech can have a huge impact. Just think of soil science – not glamorous, but it holds the key to water management and higher yields. Then there's animal nutrition, the preservation and use of genetic variety, making use of historic and wild-type relatives, and finally linking technologies. The chain from the farm to the fork has more links than you can count, and harnessing biotech to production, transport, processing, storage and packaging will have a far greater impact than cautious steps like allowing 0.1% GM products in cattle feed. Europe needs to think bigger on agriculture, and biotechnology is a great way to broaden the mind.
The demand for reliable and fast in vitro diagnostics in human medicine has increased dramatically in the last decade, while over the past few years the development and application of molecular diagnostic techniques has initiated...
The demand for reliable and fast in vitro diagnostics in human medicine has increased dramatically in the last decade, while over the past few years the development and application of molecular diagnostic techniques has initiated a revolution in the diagnosis and monitoring of infectious diseases. PCR-based systems to detect the etiologic agents of disease directly from clinical samples, without the need for culture, have been valuable in the rapid detection of uncultured or fastidious pathogens. BIORON Diagnostics GmbH in Germany provides high quality, cost- and time-effective PCR diagnostic kits to hospitals, private medical laboratories, veterinary laboratories, and other biological investigative facilities.
The two different PCR-based diagnostic lines (MultiplexLine and RealLine) cover the detection of nearly all common infectious pathogens. Further tests for cancer patients will soon be available as well.
PCR-based testing of
The MultiplexLine is focused on the detection of nosocomial infections, also known as “hospital-acquired infections”. These include MRSA, NDM-1 “superbugs” and a host of other multi-resistant bacteria. The line also includes detection kits for EHEC, STDs, TBC and intestinal bacteria. The MultiplexLine System allows the detection of more than 15 parameters in a single PCR reaction. Combined with its modular system, that makes it possible to identify the pathogen and its antibiotic resistances in one test. Because of the multi-loci PCR strategy, the risk of false or negative test results caused through mutations in the bacteria genome can be nearly 100% excluded. All diagnostic kits are currently finalising IVD CE-certification according to EC Council Directive 98/79/CE. The comfortable and simple procedure and the modest level of technical equipment needed for the MultiplexLine diagnostic makes it interesting even for small diagnostic service labs. The RealLine includes diagnostic kits for a broad range of diseases, includinginfections with HIV, HBV, HCV, STDs and tick-borne infectious diseases like TBEV and Lyme disease. The RealLine kits are striking for their simplicity: just add your sample and run PCR. The reaction mixes are lyophilised, and include all of the components needed for pathogen detection in real-time format. This makes handling convenient, and also allows transportation at room temperature and prolonged shelf-life without the loss of activity. To round out the product line, BIORON Diagnostics provides transport solution, lysis buffer and fast DNA-extraction systems for a variety of human sample material. The non-competitive internal control improves the high specificity and the validation of the reproducibility of RealLine kits.
Companion cancer diagnostics
Activating K-Ras mutations as well as epidermal growth factor receptor (EGFR) are important oncologic markers common in cancers of the pancreas, lung, colon and rectum. The results of these tests – determining whether there are mutations and if so, what kind – is crucial for patient treatment with drugs like the anti-EGFR antibodies Erbitux and Vectibix. In the absence of mutations in the K-Ras, gene treatment with anti-EGFR antibodies reduces the risk of disease progression, increasing both tumour response rate and patient survival rate. When there are activating mutations in the K-Ras gene in tumour cells, the treatment with anti-EGFR antibodies Erbitux and Vectibix will be ineffective, and not lead to positive results. BIORON Diagnostics will soon launch K-Ras and EGFR mutation detection kits by allele-specific PCR on international markets. The K-Ras kit detects seven mutations at once. For mutations of EGFR, we will offer the real-time EGFR Kit for the detection of the point mutation L858R and the EGFR Del746-750 Kit. BIORON Diagnostics puts fair trade and customer support at the top of its list of priorities. The company is currently building up international sales, and will work with distributors as well as end-users. A complete system – with detection kits, devices and training worldwide – is already available.
Contact Dr. Ferdinand Holzinger BIORON Diagnostics GmbH Rheingoenheimer Straße 36 67065 Ludwigshafen, Germany Tel.: +49-(0) 621-545900-70 Fax: +49-(0)621-545900-68
Long before hospitals had laboratories for testing human specimens – before people had even begun to dream of molecular diagnostics – physicians diagnosed diabetes by tasting the urine of their patients. Although they wouldn’t...
Long before hospitals had laboratories for testing human specimens – before people had even begun to dream of molecular diagnostics – physicians diagnosed diabetes by tasting the urine of their patients. Although they wouldn’t have described it as such, these doctors were effectively using a highly specific biosensor (the tongue) for the selective detection of a typical molecular structure in a mixture of thousands of components. This was probably the first molecular diagnostic assay of clinical value. Hundreds of years passed between the tasting test in the Middle Ages and the development of radioimmunoassays and ELISAs (Enzyme Linked Immunosorbent Assays) in the mid-20th century. But although there have been many technological advances in the last 50 years leading to a significant increase in sensitivity, specificity, speed and accuracy, the principle of selective detection of molecules through specific antibody(-ies) has remained more or less unchanged. This is why immunoassays still retain a dominant position in most diagnostic areas, among them infection serology, inflammatory diseases, cancer, cardiovascular disease, diabetes, and metabolic disorders.
Two events in the past 25 years have had a huge effect on the life sciences – in particular on biotechnology and pharma. They have also changed the diagnostics business dramatically. The invention of PCR in the 1980s revolutionized not only molecular biology, but also changed society through forensic applications, proof-of-paternity testing, detection of bioengineered foods, and many other applications. In addition, PCR enabled the Human Genome Project, which was the second event to have a massive impact on the life sciences. PCR-based diagnostics are already used frequently when treating infectious diseases. Another area in which they are now showing promise is cancer.
New technology platforms
Protagen’s UNIarray® concept is based on the fact that at some point, everyone produces antibodies against their own proteins (autoantibodies) along with those antibodies directed against pathogens such as bacteria and viruses. Autoantibody production reflects the immune response to a continuous remodeling of cells or tissues caused by continuous protein turnover and chronic disease processes. In autoimmune diseases however, some typical autoantibodies are indicative of clinical symptoms, as well as the state of the disease. In cancer, it has been shown that the presence of autoantibodies correlates with the disease without necessarily causing clinical symptoms. Autoantibody signatures detected by blood screening are therefore not only useful for the diagnosis of a disease, but can also be used for patient stratification, as well as the determination of drug responders and non-responders. Ineffective drug treatments are an enormous cost burden for both, pharma companies in drug development and health care systems. This is why clinical experts and regulatory agencies like the US FDA and the EMA are now recommending the development of diagnostic markers for companion diagnostics. This approach is the diagnostic basis of personalised medicine.
The diagnostics market –
a quick overview
The in vitro diagnostic (IVD) market can be characterised as an oligopoly. It is dominated by Roche, Abbott, Siemens, Beckman-Coulter, J&J, Biomerieux and several small to mid-sized companies. The seven largest IVD companies have about 70% of the market share. Market size in 2006 was a28.7bn and growing. The major segments of the in vitro diagnostic market include immunodiagnostics, clinical chemistry, cellular diagnostics, molecular diagnostics, microbiology, hematology, and blood banking. The in vitro diagnostics market is a mature market, and is characterised by sustained growth due to an increase in the ageing and chronically ill population. In its broader definition, ‘molecular diagnostics’ refers to the use of genomic or proteomic markers or patterns of markers for disease diagnosis or therapy decisions. Tests within this segment are beginning to contribute to advances in personalized medicine, where therapies are tailored to a patient’s individual genetic or proteomic makeup. Such tests also enable physicians to monitor the effects of treatment on the molecular properties of a disease. Forecasts say this segment will grow faster than the total market, with a CAGR of 15%.
IVD – the razor and blades model
Major IVD companies follow a particular business model. They work with machine rentals or reagent agreement plans to sell IVD assays, and necessary instrumentation is placed “free-of-charge” in the reference labs. The IVD companies then earn money by selling reagents and test kits. This means that in order to gain a return on investment in the instrumentation, the firms active in this market are forced to implement as many different assays as possible on their particular platform. It is also important that the assays are reimbursed by the health insurance providers. The main features in this business model are: – High-throughput, fully-automated analyzers with full software integration into the reference lab/core facility, with walk-away operation and many tests implemented on the same machine; closed systems, mutually exclusive. – New and upcoming assays that are continuously added to the test menu. – Marketing and direct sales to large high-throughput reference labs/hospital core facilities, competition by degree of automation and price (mostly non-exclusive analytes). – Focus is almost exclusively on assays with established reimbursement, i.e. these companies are late adopters of novel tests. – Pricing: cent – low euro value/test. – Companies: Roche, Abbott, Siemens, J&J, BioRad, Biomerieux, Qiagen,
Phadia and several others.
Business models – sales and
distribution of generic IVD-kits
Many small- to medium-sized companies manufacture test kits that can be used on open technical systems or using generic laboratory procedures. The main features in this business model are: – Open assay systems that can be combined with instrumentation such as pipetting robots and ELISA readers from multiple providers; examples are ELISA kits, line assays, lateral flow assays, microscope slides, etc. – New assays are easily added to the test menu, typically within company-specific indication niches. – Marketing and direct sales to reference labs/hospital core facilities, price competition due to non-exclusive analytes – Often assays with established reimbursement, also niche and novel assays without established reimbursement. – Low euro value/test – Companies: Phadia, Mast, Biosite,
AxisShield, Quidel, Euroimmun, Aesku, Mikrogen, DAKO, IDS, and others. In this business model, the value of the IVD assay is shared between the manufacturer, distributor, and the reference lab/hospital core facilities.
IVD-business models –
central service laboratory
Another business model has emerged in which the value of a novel test can be captured exclusively inside the company that develops and performs the test. In this relatively new business model, a few small- to medium-sized diagnostic companies are successfully offering tests in central labs without established reimbursement by health insurance providers. The prerequisite is an assay with strong performance and high clinical and patient acceptance. The main features in this business model are: – The patient sample is sent to a central lab, the assay is performed and the result is sent back to the physician, who communicates/interprets results for the patient. – Relatively new business model, more widespread in the US than in the EU. – Direct marketing to both physicians (via sales force & Internet) and patients (via Internet/PR); exclusive tests, prices up to US$3,650/test – In Germany, this is offered as “IGeL” (individuelle Gesundheitsleistung; payment by patient); it is sometimes partially paid for by private health insurances. The latter business model seems to provide the best fit for Protagen’s UNIarray® technology platform.
A Agendia B.V. Located in Amsterdam, Agendia was founded in 2002. Its products Mammaprint and Cupprint are DNA-microarray-based multiplex assays for transcription profiling. These were initially published in 2002. The tests received CE-certification in 2005 (MammaPrint, breast cancer) and 2006 (CupPrint). Tests for colon cancer are under development. The test is sold through the firm’s own and partner sales forces directly to physicians and patients. The reported prices of Agendia’s lead product “Mammaprint” (FDA clearance in 2007) range from $3,200 – $4,200 in the US or £1,650 in the UK and include sample kits and shipment costs. Agendia is a privately owned VC-funded company.
A Digene, Inc. Located in Gaithersburg in Maryland (US), Digene was founded in 1987, went public in 1996, and was acquired by Qiagen in 2007 with a headline value of US$1.6bn (55% cash, 45% Qiagen stock). It was one of the top twenty M&As in 2007. In 2006, the year before the company was acquired by Qiagen, Digene’s total sales were US$150.8m, 88% of which was in HPV testing. Sales in 2005 and 2004 were US$113.2m and US$88.9m respectively. The first HPV test was launched around 1994/1995, but the source of commercial success was the “second generation test”, which improved sensitivity and specificity. Just eight years after it was introduced in 1998, the tests were racking up > US$100m in sales. FDA approval was obtained in 2003. In 2006, Digene’s HPV test was sold directly by about 300 sales representatives worldwide. The sales force is now integrated into Qiagen.
Molecular diagnostics will play a dominating role in the future development of personalised medicines and therapies. In addition, new platform technologies with a broad applicability have evolved. They now offer exciting business opportunities, and will contribute signifi-
cantly to the future advancement of health care.
7th Berlin Conference on IP in Life Sciences: Big Data, Big Drugs
The health care industry faces significant transformation, driven by a boom in knowledge within biomedical sciences and breakthrough technologies such as gene sequencing. The management of "big data“ will change the understanding of diseases, development of drugs and treatment of patients. more